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Chronic treatment with modafinil may not be beneficial in patients with chronic fatigue syndrome

Psychopharmacology Research Unit, Centre for Neuroscience Research, King’s College London, London, UK and Respiratory Support and Sleep Centre, Papworth Hospital, Cambridge, UK

Fay H. Cafferty

MRC Biostatistics Unit, Institute of Public Health, Cambridge, UK

John M. Shneerson

Respiratory Support and Sleep Centre, Papworth Hospital, Cambridge, UK, John.Shneerson{at}papworth.nhs.uk

Ian E. Smith

Respiratory Support and Sleep Centre, Papworth Hospital, Cambridge, UK

Meirion B. Llewelyn

General Medicine/Infectious Diseases, Royal Gwent Hospital, Newport, South Wales, UK

Sandra E. File

Psychopharmacology Research Unit, Centre for Neuroscience Research, King’s College London, London, UK

Fourteen patients (7 male, 7 female, 22-63 years), classified as having chronic fatigue syndrome (CFS), but without concurrent major depression, significant sleepiness or use of psychoactive medication, completed a double-blind, placebo-controlled, crossover study of the effects of the selective wakefulness-promoting agent, modafinil (200 and 400mg/day). The treatment periods were each 20 days, with washout periods of 2 weeks. The primary aim was to determine effects on cognition and the secondary aim was to determine effects on self-ratings of fatigue, quality of life and mood. Modafinil had mixed effects in two cognitive tasks. In a test of sustained attention, treatment with 200mg reduced the latency to correctly detect sequences, but 400mg increased the number of missed targets. In a test of spatial planning, the 200mg dose resulted in a slower initial thinking time for the easiest part of the task, whereas 400mg reduced the initial thinking time for the hardest part of the test. Lastly, in a test of mental flexibility and one of motor speed, patients performed worse whilst on modafinil (400mg), compared with the placebo period. No effects were observed on the performance of other psychometric tests or on self-ratings of fatigue, quality of life or mood, but this may have been due to insufficient statistical power. It is discussed whether the limited and mixed cognitive effects that we observed could have occurred by chance, or whether a subgroup of CFS patients with daytime sleepiness would have shown greater benefits.

Key Words: chronic fatigue syndrome • modafinil • cognitive performance • sleepiness • fatigue

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